Thrombosis and failure of the hemodialysis fistula are the most common causes for hospitalization in hemodialysis patients. Diabetic hemodialysis patients have accelerated thrombosis and failure in prosthetic fistulas compared to non-diabetic patients. The roles of platelet activation and deposition within the fistula causative of thrombosis are not well defined. The goal of this study is to gain a greater understanding of these and other factors that lead to thrombosis and failure of the hemodialysis fistula in patients with renal failure. The specific aims of this study are to: 1) determine if diabetes mellitus increases platelet aggregation and deposition in hemodialysis patients, 2)determine if fistula recirculation during hemodialysis leads to platelet activation, and 3) determine if platelet inhibitors affect platelet activation and prevent fistula thrombosis. In order to satisfy these aims, platelet aggregometry will be performed using blood from non-diabetic and diabetic patients at different levels of renal function on or off dialysis. The effects of hemodialysis on platelets will be determined by detection of platelet-surface glycoproteins (GMP-140, activated IIb-IIIa) that are expressed during activation by flow cytometry and by measuring beta-thromboglobulin levels. Endothelial damage will be evaluated by measuring the release of von Willebrand factor and analysis of multimers. The deposition of platelets will be determined by imaging of the fistula and venous outflow with indium-labelled platelets. The effect of recirculation on platelet activation markers will be characterized. Using the techniques described above, the effects of aspirin, sulfinpyrazone and omega-3 fatty acid administration on platelet aggregation, activation and deposition in hemodialysis patients will be determined. The results of these studies will lead to an interventional, controlled trial of one or more of these agents directed at reduction of fistula complications. A better understanding of the pathogenesis of fistula thrombosis will lead to appropriate therapeutic interventions. Prevention of fistula thrombosis will markedly reduce morbidity in hemodialysis patients and lead to enormous cost savings.